Outline

Purpose: We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients (Wang et al., Lancet 2005, 365(9460):671). This study’s aim is to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions.

Patients and Methods: Using custom-designed Affymetrix VDX2 GeneChips we analysed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment.

Results: In this independent validation, the 76-gene signature was highly informative in identifying patients with distant metastasis within 5 years (hazard ratio, HR, 7.41; 95% confidence interval CI, 2.63-20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67-48.4). The actuarial 5 and 10-yr distant metastasis-free survival (DMFS) were 96% (95% CI, 89-99%) and 94% (95% CI, 83-98%), respectively for the good profile group and 74% (95% CI, 64-81%) and 65% (53-74%), respectively for the poor profile group. The sensitivity for 5-yr DMFS was 90%, the specificity 50%. The positive and negative predictive values were 35% (95% CI, 29-47%) and 94% (95% CI, 86-97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of ER-positive patients, pre- and postmenopausal patients, and patients with tumor sizes ≤20 mm. The subgroup of patients with ER-negative tumors was considered too small to perform a separate analysis.